(082) Effect of Suvorexant on COVID-19 Associated Delirium

Abstract:

Background: Delirium in the setting of coronavirus 2019 (COVID-19) is reportedly more common and associated with poorer overall outcomes such as lengthened hospital stays and mortality. Moreover, delirium induced by COVID-19 is heterogenous in pathogenesis and presentation, thereby complicating treatment course. Suvorexant is the first Federal Drug Administration approved dual orexin receptor antagonist hypnotic previously shown to prevent delirium and to mitigate COVID-19-induced delirium (Sher 2020). There is no widely accepted protocol to effectively treat COVID-19-induced delirium. Utilizing the framework proposed by Sher 2020, this study assessed the efficacy of suvorexant in treating delirium.

Methods: A retrospective chart review was conducted of forty inpatients who were diagnosed with COVID-19 and treated with an open-label, non-randomized combination of nightly suvorexant, in the form of a taper, and melatonin at a tertiary Virginia hospital system between October 2020 and May 2021. The Confusion Assessment Method-Severity (CAM-S) short and long forms evaluated baseline and post-suvorexant treatment delirium severity, for which patients served as their own controls. The Institutional Review Board approved this study.

Results: A paired sample t-test of 25 complete pairs demonstrated a significant difference in CAM-S scores from baseline to outcome (t(24) = 8.81, p< 0.001). For this t-test, the Cohen’s d = 1.0049, illustrating a large effect size (Fritz 2021). There was a significant decrease in CAM-S scores over this timeframe; scores decreased by 4.80 points (SD = 2.72) on average. A linear regression analysis was conducted with change in CAM-S scores as the outcome variable and predictor variables of time to evaluation and prior psychiatric history. Control variables included were: age, gender, baseline CAM-S (Dalecki 1991), suvorexant use prior to evaluation, dose of suvorexant, dose of melatonin, and use of valproic acid, haloperidol, guanfacine, or remdesivir. The analysis demonstrated no significant association of change in CAM-S score and any predictor variable.

Discussion: Several studies have reported the growing prevalence of neuropsychiatric complications in patients with COVID-19, especially delirium. This study demonstrates that the combination of a suvorexant taper, promoting sleep induction and maintenance, and steady high-dose melatonin, synchronizing circadian rhythm and decreasing inflammation, is associated with a statistically and clinically significant decrease in severity of COVID-19-induced delirium. This case series supports the exploration of the beneficial role of adding suvorexant to melatonin, neither of which impact respiratory drive, as a safe and effective treatment combination for COVID-19-induced delirium. Limitations include a non-random sample and lack of placebo control arm.

Conclusion: Given the presence of potentially new variants of COVID-19 and the growing body of literature documenting their neuropsychiatric complications, this retrospective case series provides evidence for the inclusion of suvorexant as a part of a systematic approach to treating COVID-19-induced delirium (Okino 2021, Sher 2020).